rs2232784

Variant names:

• chr19-8303874-G-A
• rs2232784
• NM_016579.4:c.483C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016579.4(CD320):​c.483C>T​(p.Ser161Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,602,380 control chromosomes in the GnomAD database, including 4,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2042 hom., cov: 33)
  • Exomes 𝑓: 0.043 (2763 hom.)
• Consequence: CD320 NM_016579.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.953
• Publications: 12 publications found

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

CD320 Gene-Disease associations (from GenCC):

• methylmalonic acidemia due to transcobalamin receptor defect

  Inheritance: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-8303874-G-A is Benign according to our data. Variant chr19-8303874-G-A is described in ClinVar as Benign. ClinVar VariationId is 136681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.953 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.483C>T	p.Ser161Ser	synonymous	Exon 3 of 5	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.357C>T	p.Ser119Ser	synonymous	Exon 2 of 4	NP_001159367.1	Q9NPF0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	ENST00000301458.10	TSL:1 MANE Select	c.483C>T	p.Ser161Ser	synonymous	Exon 3 of 5	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*771C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000471773.1	M0R1C4
	CD320	ENST00000596002.5	TSL:1	n.*771C>T		3_prime_UTR	Exon 3 of 5	ENSP00000471773.1	M0R1C4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17408 AN: 152184 Hom.: 2034 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0568 AC: 13061 AN: 229976 AF XY: 0.0515

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0633

Gnomad EAS exome AF: 0.0868

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0340

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0435 AC: 63056 AN: 1450078 Hom.: 2763 Cov.: 32 AF XY: 0.0423 AC XY: 30457 AN XY: 720494

African (AFR) AF: 0.311 AC: 10309 AN: 33178

American (AMR) AF: 0.0475 AC: 2053 AN: 43262

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1571 AN: 25842

East Asian (EAS) AF: 0.0720 AC: 2814 AN: 39062

South Asian (SAS) AF: 0.0341 AC: 2875 AN: 84208

European-Finnish (FIN) AF: 0.0282 AC: 1466 AN: 51974

Middle Eastern (MID) AF: 0.0664 AC: 382 AN: 5752

European-Non Finnish (NFE) AF: 0.0344 AC: 38026 AN: 1106876

Other (OTH) AF: 0.0594 AC: 3560 AN: 59924

GnomAD4 genome AF: 0.115 AC: 17439 AN: 152302 Hom.: 2042 Cov.: 33 AF XY: 0.113 AC XY: 8436 AN XY: 74470

African (AFR) AF: 0.303 AC: 12605 AN: 41546

American (AMR) AF: 0.0687 AC: 1052 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.0882 AC: 457 AN: 5184

South Asian (SAS) AF: 0.0393 AC: 190 AN: 4830

European-Finnish (FIN) AF: 0.0297 AC: 316 AN: 10626

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2362 AN: 68020

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.0691 Hom.: 702

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Methylmalonic acidemia due to transcobalamin receptor defect (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.80
PhyloP100		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2232784; hg19: chr19-8368758;